Post-Polycythemic Myelofibrosis: A Case Series Evaluating Incidence of Accelerated Phase, Dysmegakaryopoiesis, and Cytogenetic Abnormalities
Rachel C Ochs, Basma Basha, Susan Mathew, Daniel M Knowles, Attilio Orazi. Weill Cornell Medical College, New York, NY; Weill Cornell Medical College in Qatar, Doha, Qatar
Background: Post-polycythemic myelofibrosis (PPMF) develops during the later phase of polycythemia vera (PV) in 10-15% of patients. Accelerated phase (AP) is diagnosed in the presence of > 10% blasts in bone marrow or peripheral blood or significant myelodysplasia. AP can rapidly progress to acute myeloid leukemia (AML) which has a very poor prognosis. It is unclear how often AP occurs in patients with PPMF and what are its correlates. We investigated a cohort of patients with PPMF to assess marrow morphology and clinical and cytogenetic factors associated with reduced survival and/or AP.
Design: We studied 18 PV patients with available initial diagnostic PPMF marrow. Reticulin and trichrome stains were used to evaluate degree of fibrosis, and CD34 and CD42b to evaluate blast count and percentage of dwarf megakaryocytes respectively. Cytogenetic results were available for 16/18 patients and JAK2 mutation results were available for all patients (all mutation positive). Clinical information was obtained from outpatient electronic medical records.
Results: Patients included 10 males and 8 females, with an average age of 66.1 years. Four of eighteen (22%) patients were diagnosed with AP based on blast count (3 patients) or severe megakaryocytic dysplasia (1 patient). Four patients expired during follow-up; causes of death included AML (2 patients), T-cell lymphoma (1 patient), and myocardial infarction (1 patient). The average survival of patients in AP was 14.5 months vs. 24.1 months for non-AP patients with two deaths each occurring in the two groups with an average follow-up of 25.8 months. Dwarf megakaryocytes by CD42b >50% were associated with AP (p<0.05). Average hemoglobin and platelets, respectively, of patients surviving were 12.0 and 237 vs. 10.1 and 136.5. Two patients with AP had +8 vs. one non-AP patient. Other abnormalities included +1, 20q-, and 7q-; these were not associated with AP or increased risk of death in our patient population.
Conclusions: We show that AP occurs at high frequency in PPMF patients and is associated with short survival. An increased proportion of dwarf megakaryocytes by CD42b immunostain is significantly associated with AP, and may be useful in the evaluation of these patients along with blast count. We also found an association between low hemoglobin and platelets and reduced overall survival, similar to patients with primary myelofibrosis. In addition the presence of trisomy 8 appears to be associated with AP.
Tuesday, March 5, 2013 11:30 AM
Proffered Papers: Section C, Tuesday Morning